Ebrahim, Z; Yellon, DM; Baxter, GF; (2007) Attenuated cardioprotective response to bradykinin, but not classical ischaemic preconditioning, in DOCA-salt hypertensive left ventricular hypertrophy. PHARMACOL RES , 55 (1) 42 - 48. 10.1016/j.phrs.2006.10.004.
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Hypertensive left ventricular hypertrophy (LVH) co-exists frequently with ischaemic heart disease. While ischaemic preconditioning (IPC) is known to protect against ischaemia-reperfusion injury in LVH, it is not known if other cardioprotective manoeuvres are effective. Bradykinin, a key autacoid mediator in IPC, is protective in normal hearts but its ability to protect against ischaemia-reperfusion injury in LVH is unknown. Hypertensive LVH was induced in male rats by 4 weeks treatment with deoxycorticosterone acetate (DOCA) and salt drinking fluid. Hearts were Langendorff perfused, subjected to 35 min coronary artery occlusion and 120 min reperfusion, and infarct size (AN/RZ %) was determined by tetrazolium staining. The effects of IPC with 2 x 5 min cycles of global ischaemia or 10 min pretreatment with bradykinin were assessed. DOCA-salt rats were markedly hypertensive and left ventricle/body weight ratio was 26% greater than in normotensive controls. Baseline coronary flow and risk zone/LV ratio were similar in normotensive hearts and DOCA-salt hearts, and infarct size was similar (AN/RZ 50.6 +/- 3.2% and 47.0 +/- 3.1 %, respectively). IPC was equally protective in normotensive and DOCA-salt hearts (AN/RZ 18.6 +/- 3.3% and 18.4 +/- 2.3%, respectively, P < 0.01 versus corresponding control). Bradykinin 0.1, 0.2 or 0.5 mu M pretreatment produced concentration-dependent infarct limitation in normotensive hearts (bradykinin 0.5 mu M AN/RZ, 9.5 +/- 3.6%, P < 0.01 versus normotensive control), but the effect in DOCA-salt hearts was attenuated (bradykinin 0.5 mu M AN/RZ, 23.4 +/- 3.8%). Further, the pre-ischaemic coronary vasodilator response to bradykinin was abrogated in DOCA-salt hypertensive hearts. We conclude that the cardioprotective action of bradykinin is markedly attenuated in moderate LVH and coronary vasodilator effect is lost. The reasons for reduced sensitivity to bradykinin in the hypertensive heart are unknown but these findings may have implications for the application of preconditioning-mimetic interventions in LVH. (c) 2006 Elsevier Ltd. All rights reserved.
|Title:||Attenuated cardioprotective response to bradykinin, but not classical ischaemic preconditioning, in DOCA-salt hypertensive left ventricular hypertrophy|
|Keywords:||bradykinin, cardioprotection, DOCA-salt hypertension, hypertrophy, infarct size, ischaemia-reperfusion, ischaemic preconditioning, RAT HEARTS, NITRIC-OXIDE, MYOCARDIUM, PROTECTION, SUSCEPTIBILITY, DYSFUNCTION, PATHWAY, DISEASE|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science|
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